Variant 6-47795405-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_181744.4(OPN5):c.598A>C(p.Ile200Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000726 in 1,614,004 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00037 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00076 ( 1 hom. )

Consequence

OPN5
NM_181744.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.54

Variant links:

Genes affected

OPN5 (HGNC:19992): (opsin 5) Opsins are members of the guanine nucleotide-binding protein (G protein)-coupled receptor superfamily. This opsin gene is expressed in the eye, brain, testes, and spinal cord. This gene belongs to the seven-exon subfamily of mammalian opsin genes that includes peropsin (RRH) and retinal G protein coupled receptor (RGR). Like these other seven-exon opsin genes, this family member may encode a protein with photoisomerase activity. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2010]

OPN5 links:

OPN5 (HGNC:):

OPN5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.17156875).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OPN5	NM_181744.4 linkuse as main transcript	c.598A>C	p.Ile200Leu	missense_variant	4/7	ENST00000371211.7	NP_859528.1	Q6U736

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OPN5	ENST00000371211.7 linkuse as main transcript	c.598A>C	p.Ile200Leu	missense_variant	4/7	1	NM_181744.4	ENSP00000360255.2		Q6U736

Frequencies

GnomAD3 genomes

AF:

0.000375

AC:

AN:

152118

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000283

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000662

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000338

AC:

AN:

251368

Hom.:

AF XY:

0.000324

AC XY:

AN XY:

135860

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.0000578

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000462

Gnomad NFE exome

AF:

0.000598

Gnomad OTH exome

AF:

0.000653

GnomAD4 exome

AF:

0.000762

AC:

1114

AN:

1461886

Hom.:

Cov.:

AF XY:

0.000744

AC XY:

541

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

Gnomad4 AMR exome

AF:

0.0000671

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000337

Gnomad4 NFE exome

AF:

0.000939

Gnomad4 OTH exome

AF:

0.000745

GnomAD4 genome

AF:

0.000375

AC:

AN:

152118

Hom.:

Cov.:

AF XY:

0.000377

AC XY:

AN XY:

74312

show subpopulations

Gnomad4 AFR

AF:

0.000217

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000283

Gnomad4 NFE

AF:

0.000662

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000431

Hom.:

Bravo

AF:

0.000329

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000581

AC:

ExAC

AF:

0.000296

AC:

EpiCase

AF:

0.000600

EpiControl

AF:

0.000415

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 11, 2024

The c.598A>C (p.I200L) alteration is located in exon 4 (coding exon 4) of the OPN5 gene. This alteration results from a A to C substitution at nucleotide position 598, causing the isoleucine (I) at amino acid position 200 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.43

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.39

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.12

.;T;T;.

Eigen

Uncertain

0.28

Eigen_PC

Uncertain

0.41

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.89

D;D;.;D

M_CAP

Benign

0.0064

MetaRNN

Benign

0.17

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.0

.;L;L;.

PrimateAI

Uncertain

0.64

PROVEAN

Benign

-1.4

N;.;N;N

REVEL

Benign

0.13

Sift

Uncertain

0.012

D;.;D;D

Sift4G

Uncertain

0.033

D;.;D;D

Polyphen

0.83

.;P;P;.

Vest4

0.46

MVP

0.34

MPC

1.0

ClinPred

0.25

GERP RS

5.9

Varity_R

0.25

gMVP

0.83

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over